Use of 1-hydroxy-2-pyridones for the treatment of seborrheic dermatitis

ABSTRACT

Compounds of the formula (I) are disclosed and are suitable for the treatment of seborrheic dermatitis.

[0001] Seborrheic dermatitis is understood as meaning a disorder of thescalp which differs from simple dandruff by the presence of erythema asa sign of inflammation, by the greater degree of scaling with occasionalitching and burning, and by the occurrence of eczematous changes toother body sites. It can occur in the form of patches, but also morefrequently affects the whole scalp and often includes, beyond thehairline, the forehead, around the neck and the ears. In severe cases,the scalp can have a secondary infection, and the changes can thenexhibit a spongy consistency, vesicle and crust formation and can weep.

[0002] Seborrheic dermatitis frequently occurs even in infancy andusually remits spontaneously at an age of 8-12 months. The scalp changesconsisting of erythema, scaling and occasionally vesicles and crusts ininfants can regress spontaneously within a few weeks, intermittentlyreoccur or persist during the entire childhood. They are frequentlycombined with a similar. process around the eyelids, nose and ears.Later, the condition usually occurs after puberty and can last for thewhole life or even increase in strength. Approximately 1-3% of thepopulation are affected by this illness.

[0003] It is known that 1-hydroxy-2-pyridones and their salts exhibitactivity against normal dandruff which is characterized by a clinicallynoninflammatory scaling of the scalp occurring in nearly all people (DE22 34 009).

[0004] The most promising type of treatment of seborrheic dermatitisuntil now was the topical application of corticosteroid preparations,but more recently topical therapy with antimycotic substances has gainedimportance.

[0005] While corticosteroid preparations display their activityexclusively via an effect on the inflammatory process, the antimycoticsubstances such as ketoconazole are active exclusively against the yeastfungi of the strain Pityrosporum which is assumed to be the cause ofseborrheic dermatitis. The 1-hydroxy-2-pyridones according to theinvention, however, combine the properties of both classes of substancein one substance and exhibit both antiinflammatory action andantimycotic activity against Pityrosporum strains.

[0006] In comparison to ketoconazole, the substances according to theinvention —even afteronly a short topical contact time—concentraterapidly in the skin layers which are relevant for fungal growth and thuscontribute to a rapid cure.

[0007] While ketoconazole is inactive in vitro against gram-positivebacteria (Kinsman et al., J. Med. Microbiol. (1983) 16, No. 2, IV), thehydroxy-pyridones according to the invention exhibit activity againstgram-positive and gram-negative aerobic and anaerobic bacteria (Dittmaret al., Arzneim.-Forschung, (1981) 31 (11), No. 8a, pp. 1317-1322). Withrespect to the treatment of secondarily infected cases, this is anextremely important finding.

[0008] Compared with ketoconazole, the compounds used according to theinvention furthermore have very crucial. advantages with respect totheir processing possibilities in pharmaceutical preparations. Onaccount of their solubility in water, alcohols and aqueous-alcoholicsolutions, the preparation of hair lotions and transparent gelpreparations is possible without problems.

[0009] The preparations according to the invention can also be employedfor the treatment of Pityriasis versicolor, a superficial,noninflammatory skin fungus disorder on the trunk.

[0010] The invention therefore relates to the use of1-hydroxy-2-pyridones of the formula I

[0011] in which R¹, R² and R³, which are identical or different, are ahydrogen atom or alkyl having 1-4 carbon atoms, and

[0012] R⁴ is a saturated hydrocarbon radical having 6 to 9 carbon atomsor a radical of the formula II

[0013] where

[0014] X is S or O,

[0015] Y is a hydrogen atom or up to 2 halogen atoms such as chlorineand/or bromine,

[0016] Z is a single bond or the bivalent radicals O, S, —CR²—(R═H or(C₁-C₄)-alkyl) or other bivalent radicals having 2-10 carbon and, ifappropriate, oxygen and/or sulfur atoms linked in the form of a chain,where—if the radicals contain 2 or more oxygen and/or sulfur atoms—thelatter must be separated from one another by at least 2 carbon atoms andwhere 2 adjacent carbon atoms can also be linked to one another by adouble bond and the free valences of the carbon atoms are saturated by Hand/or (C₁-C₄)-alkyl groups,

[0017] Ar is an aromatic ring system having up to two rings which can besubstituted by up to three radicals from the group consisting offluorine, chlorine, bromine, methoxy, (C₁-C₄)-alkyl, trifluoromethyl andtrifluoromethoxy, in free or in salt form,

[0018] for the production of a pharmaceutical for the treatment ofseborrheic dermatitis.

[0019] In the radicals “Z”, the carbon chain members are preferably CH₂groups. If the CH₂ groups are substituted by C₁-C₄-alkyl groups, CH₃ andC₂H₅ are preferred substituents. Exemplary radicals “Z” are:

[0020] —O—, —S—, —CH₂—, —(CH₂)_(m)—(m=2-10), —C(CH₃)₂—, —CH₂O—, —OCH₂—,—CH₂S—, —SCH₂—, —SCH(C₂H₅)—, —CH═CH—CH₂O—, —O—CH₂—CH═CH—CH₂O—,—OCH₂—CH₂O—, —OCH₂—CH₂CH₂O—, —SCH₂CH₂CH₂S—, —SCH₂CH₂CH₂CH₂O—,—SCH₂CH₂OCH₂CH₂O —, —SCH₂CH₂OCH₂CH₂O —CH₂CH₂S— or —S—CH₂—C(CH₃)₂—CH₂—S—.

[0021] The radical “S” is a sulfur atom, the radical “O” is an oxygenatom. The term “Ar” denotes phenyl or fused systems such as naphthyl,tetrahydro- naphthyl and indenyl, and also isolated systems as such,which are derived from biphenyl, diphenylalkanes, diphenyl ethers anddiphenyl thioethers.

[0022] In the formula I, the hydrocarbon radial R⁴ is an alkyl orcyclohexyl radical which can also be bonded to the pyridone ring via amethylene or ethylene group or can contain an endomethyl group. R⁴ canalso be an aromatic radical which, however, is preferably bonded to thepyridone radical via at least one aliphatic carbon atom.

[0023] Important representatives of the class of compounds characterizedby the formula I are:

[0024]6-[4-(4-chlorophenoxy)phenoxymethyl]-1-hydroxy-4-methyl-2-pyridone,6-[4-(2,4-dichlorophenoxy)phenoxymethyl]-1-hydroxy4-methyl-2-pyridone,6-(biphenyl4-oxymethyl)-1-hydroxy4-methyl-2-pyridone,6-(4-benzyl-phenoxymethyl)-1-hydroxy4-methyl-2-pyridone,6-[4-(2,4-dichlorobenzyl-oxy)phenoxymethyl]-1-hydroxy4-methyl-2-pyridone,6-[4-(4-chloro-phenoxy)phenoxymethyl]-1-hydroxy-3,4-dimethyl-2-pyridone,6-[4-(2,4-dichlorobenzyl)phenoxymethyl]-1-hydroxy-3,4-dimethyl-2-pyridone,6-[4-cinnamyloxy)phenoxymethyl]-1-hydroxy4-methyl-2-pyridone,1-hydroxy4-methyl-6-[4-(4-trifluoromethylphenoxy)phenoxymethyl]-2-pyridone,1hydroxy-4-methyl-6-cyclohexyl-2-pyridone,1-hydroxy4-methyl-6-(2,4,4-trimethylpentyl)-2-pyridone,1-hydroxy4-methyl-6-n-hexyl-, -6-iso-hexyl-, -6-n-heptyl- or-6-isoheptyl-2-pyridone, 1-hydroxy4-methyl-6-octyl- or-6-isooctyl-2-pyridone, in particular1-hydroxy4-methyl-6-cyclohexyl-methyl- or -6-cyclohexylethyl-2-pyridone,where the cyclohexyl radical can in each case also carry a methylradical, 1-hydroxy4-methyl-6-(2-bicyclo-[2,2,1]heptyl)-2-pyridone,1-hydroxy-3,4-dimethyl-6-benzyl- or -6-dimethyl-benzyl-2-pyridone or1-hydroxy4-methyl-6-(β-phenylethyl)-2-pyridone.

[0025] The term “saturated” in this case designates those radicals whichcontain no aliphatic multiple bonds, i.e. no ethylenic or acetylenicbonds.

[0026] The abovementioned compounds of the formula I can be employedeither in free form or as salts, use in free form is preferred.

[0027] If organic bases are used, poorly volatile bases are preferablyemployed, for example low molecular weight alkanolamines such asethanolamine, diethanolamine, N-ethylethanolamine,N-methyidiethanolamine, triethanol-amine, diethylaminoethanol,2-amino-2-methyl-n-propanol, dimethylamino-propanol,2-amino-2-methylpropanediol, triisopropanolamine. Further poorlyvolatile bases which may be mentioned are, for example, ethylenediamine,hexamethylenediamine, morpholine, piperidine, piperazine,cyclohexylamine, tributylamine, dodecylamine, N,N-dimethyldodecylamine,stearylamine, oleylamine, benzylamine, dibenzylamine,N-ethylbenzylamine, dimethylstearylamine, N-methylmorpholine,N-methylpiperazine, 4-methylcyclohexylamine, N-hydroxyethylmorpholine.The salts of quaternary ammonium hydroxides such astrimethylbenzylammonium hydroxide, tetramethylammonium hydroxide ortetraethylammonium hydroxide can also be used, furthermore guanidine andits derivatives, in particular its alkylation products. However, it isalso possible to employ as salt-forming agents, for example, lowmolecular weight alkylamines such as methylamine, ethylamine ortriethylamine. Suitable salts for the compounds to be employed accordingto the invention are also those with inorganic cations, for examplealkali metal salts, in particular sodium, potassium or ammonium salts,alkaline earth metal salts such as, in particular, the magnesium orcalcium salts, as well as salts with bi- or tetravalent cations, forexample the zinc, aluminum or zirconium salt.

[0028] The active compounds to be employed in the preparations of thecompound of the formula I can be prepared, for example, according toprocesses given in U.S. Pat. No. 2,540,218.

[0029] For the use according to the invention of the compoundsmentioned, liquid to semisolid pharmaceutical preparations, inparticular hair lotions, shampoos, liquid soaps, as well as cream,ointment and gel preparations, are suitable.

[0030] In this case, these are always preparations which, depending ontheir actual intended use, are applied to the skin and/or to the scalpfor a shorter or longer time. Due to the addition of the compoundsaccording to the invention, an effective treatment of the seborrheicdermatitis is brought about.

[0031] If the preparations according to the invention are present asshampoo, they can be in clear liquid or opaque liquid form, in creamform or even gelatinous. The surfactants on which these shampoos arebased can be of anionic, cationic, nonionic or amphoteric nature and canalso be present as a combination of these substances.

[0032] Preferably, however, anionic surfactants are employed on theirown or as a mixture with other anionic surfactants as base surfactants -if appropriate with addition of amphoteric surfactants as cosurfactant.

[0033] As the sole detergent substances, amphoteric surfactants arevirtually insignificant, since their foaming behavior, thickenabilityand partly also skin and eye mucous membrane tolerability are onlymoderate. In combination with various anionic surfactants, however,precisely these properties are synergistically improved. This explainsthe relatively great importance of the amphoteric surfactants for theoptimization of anionic shampoo bases.

[0034] Nonionic surfactants can also be employed as cosurfactants.

[0035] Examples of anionic detergent substances of this type which maybe mentioned are: (C₁₀-C₂₀)-alkyl- and -alkylenecarboxylates, alkylether carboxylates, fatty alcohol sulfates, fatty alcohol ethersulfates, alkylol-amide sulfates and sulfonates, fatty acid alkylamidepolyglycol ether sulfates, alkanesulfonates and hydroxyalkanesulfonates,olefinsulfonates, acyl esters of isothionates, α-sulfofatty acid esters,alkylbenzosulfonates, alkylphenol glycol ether sulfonates,sulfosuccinates, sulfosuccinic acid hemiesters and diesters, fattyalcohol ether phosphates, protein-fatty acid condensation products,alkylmonoglyceride sulfates and sulfonates, alkylglyceride ethersulfonates, fatty acid methyltaurides, fatty acid sarcosinates orsulforicinoleates. These compounds and their mixtures are used in theform of their water-soluble or water-dispersible salts, for example thesodium, potassium, magnesium, ammonium, mono-, di- andtriethanolammonium as well as analogous alkylolammonium salts.

[0036] Examples of amphoteric surfactants which can be added to theshampoos are: N-((C₁₂-C₁₈)-alkyl)-β-aminopropionates andN-((C₁₂-C₁₈)-alkyl)-β-iminodipropionates as alkali metal and mono-, di-and trialkylol-ammonium salts;N-acylamidoalkyl-N,N-dimethylacetobetaine, preferablyN-((C₈-C₁₈)-acyl)amidopropyl-N,N-dimethylacetobetaine;(C₁₂-C₁₈)-alkyl-dimethylsulfopropylbetaine; amphoteric surfactants basedon imidazoline (trade name: Miranol®, Steinapon®), preferably the sodiumsalt of1-(β-carboxymethyloxyethyl)-1-(carboxymethyl)-2-laurylimidazolinium;amine oxides, e.g. (C₁₂-C₁₈)-alkyldimethylamine oxide or fatty acidamidoalkyldimethylamine oxide.

[0037] Suitable nonionic surfactants which can be employed as detergentsubstances are, for example: fatty alcohol ethoxylates (alkylpolyethylene glycols); alkylphenol polyethylene glycols; alkylmercaptan.polyethylene glycols; fatty amine ethoxylates (alkylamino polyethyleneglycols); fatty acid ethoxylates (acyl polyethylene glycols),polypropylene glycol ethoxylates (Pluronic®); fatty acid alkylolamides(fatty acid amide polyethylene glycols); sucrose esters; alkylpolyglucosides; sorbitol esters and polyglycol ether.

[0038] Suitable cationic surfactants are, for example, quaternaryammonium salts such as di-((C₁₀-C₂₄)-alkyl)dimethylammonium chloride orbromide, preferably di-((C₁₂-C₁₈)-alkyl)dimethylammonium choride orbromide; (C₁₀-C₂₄)-alkyldimethylethylammonium chloride or bromide;(C₁₀-C₂₄)-alkyltrimethylammonium chloride or bromide, preferablycetyltrimethyl-ammonium chloride or bromide and(C₂₀-C₂₂)-alkyltrimethylammonium chloride or bromide;(C₁₀-C₂₄)-alkyldimethylbenzylammonium chloride or bromide; preferably(C₁₂-C₁₈)-alkyldimethylbenzylammonium chloride;N-((C₁₀-C₁₈)-alkyl)pyridinium chloride or bromide, preferablyN-((C₁₂-C₁₆)-alkyl)pyridinium chloride or bromide;N-((C₁₀-C₁₈)-alkyl)isoquinolinium chloride, bromide or monoalkylsulfate;N-((C₁₂-C₁₈)-alkylolaminoformyl-methyl)pyridinium chloride;N-((C₁₂-C₁₈)-alkyl)-N-methylmorpholinium chloride, bromide ormonoalkylsulfate, N-((C₁₂-C₁₈)-alkyl)-N-ethyl-morpholinium chloride,bromide or monoalkylsulfate; (C16-C₁₈)-alkyl-pentaoxethylammoniumchloride; diisobutylphenoxyethoxyethyldimethyl-benzylammonium chloride;salts of N,N-diethylaminoethylstearylamide and -oleylamide withhydrochloric acid, acetic acid, lactic acid, citric acid, phosphoricacid; N-acylamidoethyl-N,N-diethyl-N-methylammonium chloride, bromide ormonoalkylsulfate and N-acylamidoethyl-N,N-diethyl-N-benzylammoniumchloride, bromide or monoalkylsulfate, where acyl is preferably stearylor oleyl.

[0039] The preparations according to the invention can additionallycontain further additives, e.g. aromatic substances, cblorants,opacifiers and pearl luster agents, for example esters of fatty acidsand polyols, magnesium and zinc salts of fatty acids, dispersions basedon copolymers, thickeners such as sodium, potassium or ammoniumchloride, sodium sulfate, fatty acid alkylolamides, cellulosederivatives of natural gums, collagen hydrolyzates, furthermore fats,oils, fatty alcohols, silicones, substances having a keratolytic andkeratoplastic action. for example sulfur, salicylic acid or enzymes.

[0040] The shampoos are prepared in a manner known per se by mixingtogether of the individual components and a further processing—ifnecessary —suited to the particular type of preparation. Some of thesevarious possible preparations are described by way of example in theworking examples.

[0041] The preparations according to the invention can also be presentin the form of aqueous and aqueous-alcoholic hair lotions, and alsothose in gel form and in aerosol form as spray or foam. Alcoholsemployed are preferably ethanol and isopropyl alcohol.

[0042] Further preparations which may be mentioned in which the1-hydroxy-2-pyridones can be used according to the invention are, forexample, cream and ointment preparations, products which are primarilyused for the treatment of hairless head and body parts.

[0043] The preparation of all these preparations is also carried out—asalready mentioned in the case of shampoo—in a manner known per se withaddition of the active compound employed according to the invention. Ofthe abovementioned 1-hydroxy-2-pyridones, the preparations according tothe invention can contain one compound or even several in combination.

[0044] The pH of the preparations is in the skin-physiological range ofapproximately pH 4.5 to 6.5. Whereas, when using the compounds in saltform, the adjustment of the pH range mentioned has to be carried outusing organic acids, this measure is not necessary when using the freecompounds.

[0045] In the preparations according to the invention, the activecompounds is incorporated in amounts which are customarily betweenapproximately 0.05 and approximately 10%. Within this range, theconcentrations of the specific preparations depend on their intendeduse. Certain preparation forms such as concentrates, which are to bediluted before use, can have considerably higher concentrations.

[0046] If they are preparations which remain on the skin and on thescalp, for example gel preparations, ointments, creams or hair lotions,lower concentrations will be employed, for example from about 0.05% toabout 1%, preferably from 0.1 to 0.5%. In higher concentrations, theywill expediently be used when they are preparations which, optionallyafter dilution, only act on the scalp for a short time, for exampleshampoos or liquid soaps. In these cases, for example, concentrations ofapproximately 0.2 to approxi- mately 10%, preferably from approximately0.5% to approximately 2%, can be expedient.

[0047] The following quantitative data relate to the weight, if notstated otherwise.

EXAMPLE 1

[0048] A preparation according to the invention has the followingcomposition:

[0049] Shampoo (based on anionic detergent substances)1-Hydroxy-4-methyl-6-cyclohexyl-2(1H)pyridone  1.00% Sodium lauryldiglycol ether sulfate (27% strength solution) 40.00% Disodium laurylpolyglycol ether sulfosuccinate (33% strength 10.00% solution) Sodiumchloride  2.50% Water 46.50%

EXAMPLE 2

[0050] A preparation according to the invention has the followingcomposition:

[0051] Shampoo (based on anionic detergent substance with amphotericsurfactant as cosurfactant)1-Hydroxy-4-methyl-6-cyclohexyl-2(1H)pyridone  1.00% Sodium lauryldiglycol ether sulfate (27% strength solution) 36.00%Cocamidopropylbetaine (30% strength solution)  6.00% Sodium chloride 3.30% Water 53.70%

EXAMPLE 3

[0052] A preparation according to the invention has the followingcomposition:

[0053] Shampoo (based on anionic detergent substance with nonionicsurfactant as cosurfactant)1-Hydroxy-4-methyl-6-cyclohexyl-2(1H)pyridone  1.50% Sodium lauryldiglycol ether sulfate (27% strength solution) 30.00% Lauryl alcoholpolyglucoside  8.00% Sodium chloride  2.00% Water 58.50%

EXAMPLE 4

[0054] A preparation according to the invention has the followingcomposition:

[0055] Liquid soap 1-Hydroxy-4-methyl-6-cyclohexyl-2(1H)pyridone  1.00%Sodium lauryl diglycol ether sulfate (27% strength solution) 35.00%Cocamidopolyglycol ether sulfate magnesium salt (30% strength  8.00%solution) Cocamidopropylbetaine (30% strength solution) 10.00% Laurylalcohol glycol ether  2.00% Sodium chloride  2.00% Water 42.00%

EXAMPLE 5

[0056] A preparation according to the invention has the followingcomposition:

[0057] Hair lotion1-Hydroxy-4-methyl-6-[4-(4-chlorophenoxy)phenoxymethyl]-  0.05%2(1H)pyridone 2-Propanol 60.00% Water 39.95%

EXAMPLE 6

[0058] A preparation according to the invention has the followingcomposition:

[0059] Gel preparation 1-Hydroxy-4-methyl-6-cyclohexyl-2(1H)pyridone 0.75% 2-Propanol 15.00% 2-Octyldodecanol  7.50% Carbomer 4,000,000 0.50% Polysorbate 60  1.50% Sodium hydroxide  0.18% Water 74.57%

EXAMPLE 7

[0060] A preparation according to the invention has the followingcomposition:

[0061] Cream preparation 1-Hydroxy-4-methyl-6-cyclohexyl-2(1H)-pyridone, 1.00% aminoethatnol salt 1:1 2-Octyldodecanol  7.50% Liquid paraffin 7.50% Stearyl alcohol  7.50% Cetyl alcohol  7.50% Polysorbate 60  3.00%Sorbitan monostearate  2.00% Lactic acid, 90% strength  0.51% Water63.49%

EXAMPLE 8

[0062] In a clinical study with a total of 180 patients, it was possibleto show that the symptoms of seborrheic dermatitis of the scalp (severescaling, inflammation, itching) can be effectively treated by a1-2×weekly treatment with a 1% strength ciclopirox shampoo preparationover a period of 4 weeks.

EXAMPLE 9

[0063] In a clinical study, it was possible to successfully treat 180patients with seborrheic dermatitis of the scalp, of the face and of theupper body by application of a 0.77% strength ciclopirox gel preparationover a period of 4 weeks.

1. The use of 1-hydroxy-2-pyridones of the formula I

in which R¹, R² and R³, which are identical or different, are a hydrogenatom or alkyl having 1-4 carbon atoms, and R⁴ is a saturated hydrocarbonradical having 6 to 9 carbon atoms or a radical of the formula II

where X is S or O, Y is a hydrogen atom or up to 2 halogen atoms such aschlorine and/or bromine, Z is a single bond or the bivalent radicals O,S, —CR²—(R═H or (C₁-C₄)-alkyl) or other bivalent radicals having 2-10carbon and, if appropriate, oxygen and/or sulfur atoms linked in theform of a chain, where—if the radicals contain 2 or more oxygen and/orsulfur atoms—the latter must be separated from one another by at least 2carbon atoms and where 2 adjacent carbon atoms can also be linked to oneanother by a double bond and the free valences of the carbon atoms aresaturated by H and/or (C₁-C₄)-alkyl groups, Ar is an aromatic ringsystem having up to two rings which can be substituted by up to threeradicals from the group consisting of fluorine, chlorine, bromine,methoxy, (C₁-C₄)-alkyl, trifluoromethyl and trifluoromethoxy, in free orin salt form, for the production of a pharmaceutical for the treatmentof seborrheic dermatitis.
 2. The use as claimed in claim 1, wherein thecompound of the formula I is employed in which Ar is a bicyclic systemwhich is derived from biphenyl, diphenylalkane or diphenyl ether.
 3. Theuse as claimed in claim 1 or 2, wherein the compound of the formula Icontains a cyclohexyl radical in the position R⁴.
 4. The use as claimedin one or more of claims 1 to 3, wherein the compound of the formula Icontains an octyl radical of the formula —CH₂—CH(CH₃)—CH₂—C(CH₃)₃ in theposition R⁴.
 5. The use as claimed in claim 1, wherein1-hydroxy-4-methyl-6-[4-(4-chlorophenoxy)phenoxymethyl]-2(1H)pyridone,1-hydroxy-4-methyl-6-cyclohexyl-2(1H)pyridone or1-hydroxy-4-methyl-6-(2,4,4-trimethylpentyl)-2(1H)pyridone is employed.6. The use as claimed in one or more of claims 1 to 5, wherein thepharmaceutical is a hair lotion, shampoo or a cream, ointment or gelpreparation.
 7. The use as claimed in claim 6, wherein anionic,cationic, nonionic or amphoteric surfactants are employed on their ownor as a mixture with other surfactants.
 8. The use as claimed in claim7, wherein the surfactant employed is at least one anionic surfactant onits own or as a mixture with other anionic surfactants and/or amphotericsurfactants.
 9. The use as claimed in one or more of claims 1 to 8,wherein the pharmaceutical has a pH of 4.5 to 6.5.
 10. A pharmaceuticalpreparation comprising a 1-hydroxy-2-pyridone of the formula I asclaimed in claim 1 and at least one anionic, cationic, nonionic oramphoteric surfactant or a mixture of these surfactants.
 11. Apharmaceutical preparation as claimed in claim 10, wherein thesurfactant employed is at least one anionic surfactant on its own or asa mixture with other anionic surfactants and/or amphoteric surfactants.12. A pharmaceutical preparation as claimed in claim 10 or 11, whereinthe preparation has a pH of 4.5 to 6.5.
 13. A pharmaceutical preparationas claimed in one or more of claims 10 to 12, wherein the1-hydroxy-2-pyridone of the formula I is employed in a concentration of0.2% to 10%, preferably of 0.5% to 2%.